The general purpose of this research is to establish electrophysiologic correlates of psychiatric illness. Such correlates may then serve to focus animal research on underlying mechanisms. EEG and evoked potential (EP) data are obtained in different clinical groups and analyzed in various ways with computer assistance. Patients are followed through treatment with serial determinations to assess the effects of drugs. The main EP experimental procedure currently employed involves pseudorandomized presentation of electrical pulses to right and left wrists, full field visual checkerboard flash, binaural click, with monopolar recording from 15 leads; on-line averaging is in two modes, to assess short- and longer term variability. EEGs are subjected to coherence, power spectrum, and amplitude and frequency time series analyses. EPs were analyzed for amplitude, latency, and waveshape stability. Reduced data are treated statistically with multivariate procedures. Some recent results of interest are: a) Confirmation of previous findings showing that, before 100 msec poststimulus, somatosensory EP amplitude and waveshape stability were greater than normal in chronic schizophrenics, while they were less than normal after 100 msec; however, although similar for later EP events, the early epoch differences did not hold for auditory and visual EPs. b) Spatial distributions of various EP peaks differed between schizophrenic and depressive psychoses and both psychoses also differed from normal. c) EP waveshape stability measures for the two brain hemispheres were generally more asymmetrical than normal in schizophrenic and depressive psychotic patients; where deviant, the left hemisphere was more unstable in the psychoses. d) Lithium carbonate augmented amplitude of positive and decreased amplitude of negative EP peaks. To further investigate the deviant distribution of brain activity suggested by the EP topographic findings, an 8-channel rheoencephalographic recorder has been developed to provide measures reflecting regional cerebral blood flow.